P. nigrum L. extracts and the piperine alkaloid have important antimicrobial, anti-inflammatory, and antioxidant properties. Therefore, in this study, we evaluated the antimicrobial activity and cytotoxicity of P. nigrum L. extracts and piperine, a compound isolated from the extracts of P. nigrum L. Extracts obtained via maceration, soxhlet, and purification steps, in addition to isolated piperine, were used in this study. Spectroscopic methods, such as nuclear magnetic resonance, scanning electron microscopy, X-ray diffraction, thermogravimetry, and differential scanning calorimetry, were used to characterize piperine. In the microbiological analyses, the extract obtained via maceration-derived sample showed high efficiency in inhibiting Salmonella spp. (MIC < 100 μg/mL). The extract obtained via a soxhlet-derived sample showed promising inhibitory activity against almost all microorganisms, with negligible inhibition of Pseudomonas aeruginosa. Favorable inhibition coefficients were also observed against Staphylococcus aureus and Salmonella spp. (MIC < 100 μg/mL) for the extract obtained via purification of the steps-derived sample. Piperine showed an excellent inhibition coefficient against most microorganisms, with inactivity only observed against P. aeruginosa. Cytotoxicity evaluation assays in cancer cell lines revealed that piperine exhibited inhibitory potential on all tested tumor cell lines, causing a decrease in cell viability and achieving an IC50 of less than 30 μg/mL. The analyzed extracts from P. nigrum L. seeds showed cytotoxic activity against tumor and non-tumor cell lines.

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Gastric cancer is one of the most frequent types of neoplasms worldwide, usually presenting as aggressive and difficult-to-manage tumors. The search for new structures with anticancer potential encompasses a vast research field in which natural products arise as promising alternatives. In this scenario, piperine, an alkaloid of the Piper species, has received attention due to its biological activity, including anticancer attributes. The present work proposes three heating-independent, reliable, low-cost, and selective methods for obtaining piperine from Piper nigrum L. (Black pepper). Electronic (SEM) and optical microscopies, X-ray diffraction, nuclear magnetic resonance spectroscopies (13C and 1H NMR), and optical spectroscopies (UV–Vis, photoluminescence, and FTIR) confirm the obtention of piperine crystals. The MTT assay reveals that the piperine samples exhibit good cytotoxic activity against primary and metastasis models of gastric cancer cell lines from the Brazilian Amazon. The samples showed selective cytotoxicity on the evaluated models, revealing higher effectiveness in cells bearing a higher degree of aggressiveness. Moreover, the investigated piperine crystals demonstrated the ability to act as a good cytotoxicity enhancer when combined with traditional chemotherapeutics (5-FU and GEM), allowing the drugs to achieve the same cytotoxic effect in cells employing lower concentrations. These results establish piperine as a promising molecule for therapy investigations in aggressive gastric cancer, both in its isolated form or as a bioenhancer.

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